. This prospective epidemiologic and neuropsychological study will examine the effects of early brain damage on selected aspects of cognitive development. Two brain insults associated with preterm birth, neonatal white matter damage (WMD) and transient hypothyroxinemia of prematurity (THP), have been shown to be strong predictors of motor disability and to be associated with poor general developmental outcome; nevertheless, their effects on specific aspects of cognitive development are unknown. In order to investigate the long-term cognitive effects of WMD and THP, a sample of 597 surviving children from the Developmental Epidemiology Network (DEN) cohort of very low birth weight (<1501 g) infants will be recruited for thorough neuropsychological evaluation at age six years. Extensive perinatal and early postnatal data are available for these children, including the evidence of THP and detailed ultrasound evaluations of WMD. The entire sample to be followed will be given thorough neuropsychological evaluations. Cranial magnetic resonance imaging (MRI) and functional MRI will be undertaken for selected sub-samples. The Specific Aims are to investigate: 1) independent neuropsychological effects of neonatal WMD and THP; 2) the role of other predictors of neuropsychological function (specifically, motor and sensory impairments and socioeconomic environment); 3) structural evidence of WMD at age 6 and associated neuropsychological outcomes; and 4) evidence of the plasticity of the developing brain in the presence of neonatal WMD. The health significance of this research lies in its potential to improve the understanding and prediction and ultimately, the prevention of long-term functional sequelae of brain injuries sustained by infants born prematurely.